Apparatuses and methods for suspending and washing the contents of a plurality of cuvettes

ABSTRACT

Apparatuses and methods for washing a plurality of fluid samples are disclosed herein. In an embodiment, a system for washing a plurality of fluid samples respectively located within a plurality of cuvettes includes a rotor configured to rotate the plurality of cuvettes about an axis, a traveler mechanism located beneath the rotor, the traveler mechanism configured to move a plurality of magnets parallel to the axis of rotation of the rotor to position the plurality of magnets so that each cuvette of the plurality of cuvettes is located adjacent to at least one magnet of the plurality of magnets, and a wash system located above the rotor, the wash system configured to at least one of inject fluid into or aspirate fluid from the plurality of the cuvettes, while the plurality of magnets suspend magnetic particles located within each of the plurality of cuvettes.

PRIORITY CLAIM

This application is a divisional application of U.S. patent applicationSer. No. 15/553,504, filed Aug. 24, 2017, now U.S. Pat. No. 10,948,505,which is a national phase entry of PCT App. No. PCT/US2016/19392, filedFeb. 24, 2016, which claims the benefit of U.S. Provisional App. No.62/126,104, filed Feb. 27, 2015, the entire disclosures each of which isincorporated herein by reference.

FIELD OF THE DISCLOSURE

The present disclosure relates generally to methods and apparatuses forsuspending and washing the contents of a plurality of cuvettes, and morespecifically to a rotor, traveler mechanism and multi-wash mechanismthat work in conjunction to quickly and efficiently suspend and wash thecontents of a plurality of cuvettes.

BACKGROUND

Many immunochemistry analysis systems require that analyte molecules ina patient's biological sample (e.g. serum or plasma) attach toparamagnetic particles. Such systems require that magnets be positionedso that the paramagnetic particles can be localized and one or morewashing steps can be performed to remove background signals associatedwith potential contaminants and interfering substances that may bepresent in samples.

The analyses performed by these systems, however, are relatively slowbecause the equipment required is bulky and it is difficult to bothlocalize paramagnetic particles and wash a plurality of samples at thesame time. There is accordingly a need for equipment that streamlinesthis process, that is, efficiently localizes the paramagnetic particlesin a plurality of cuvettes so that the washing steps can be performedwhile the paramagnetic particles are localized.

Older systems have exhibited performance problems including unacceptablylong collection times, beads failing to stay on the magnets during wash,and non-resuspendability of the beads in the next step—stronger magnetsbenefit the first and second of these, but impact the third. Thus asuccessful system must provide the best balance of magnet strength andduration of collection.

SUMMARY

The present disclosure is directed to apparatuses and methods forwashing a plurality of fluid samples respectively located within aplurality of cuvettes. In a general embodiment, a system for washing aplurality of fluid samples includes a rotor configured to rotate theplurality of cuvettes about an axis, a traveler mechanism locatedbeneath the rotor, the traveler mechanism configured to move a pluralityof magnets parallel to the axis of rotation of the rotor to position theplurality of magnets so that each cuvette of the plurality of cuvettesis located adjacent to at least one magnet of the plurality of magnets,and a wash system located above the rotor, the wash system configured toat least one of inject fluid into or aspirate fluid from the pluralityof the cuvettes, while the plurality of magnets suspend magneticparticles located within each of the plurality of cuvettes.

In another embodiment, the axis of rotation of the rotor is a verticalaxis.

In another embodiment, the wash system is configured to inject fluidinto and aspirate fluid from the plurality of the cuvettes.

In another embodiment, the plurality of magnets includes a plurality offirst magnets with a first polarity and a plurality of second magnetswith an opposite second polarity.

In another embodiment, the traveler system is configured to position theplurality of magnets so that each of the plurality of cuvettes has afirst magnet on a first side and a second magnet on an opposite secondside.

In another embodiment, the wash system includes a plurality of probesconfigured to at least one of inject fluid into or aspirate fluid fromthe plurality of the cuvettes.

In another embodiment, the probes each include a first portion toaspirate fluid from a respective cuvette and a second portion to injectfluid into the respective cuvette.

In another embodiment, the wash system includes a probe positioningsensor configured to determine if at least one of the probes ismisaligned.

In another embodiment, the traveler mechanism includes a guide rail anda sliding device, and the sliding device translates along the guide railto position the plurality of magnets so that each cuvette of theplurality of cuvettes is located adjacent to at least one magnet of theplurality of magnets.

In another embodiment, the sliding device includes a base portion and amagnet holder, the base portion is moveable along the guide rail, andthe magnet holder is separately moveable with respect to the baseportion.

In another embodiment, the plurality of magnets is positioned in an arcthat corresponds to an arc of the plurality of cuvettes located on therotor.

In a general embodiment, a system for washing a plurality of fluidsamples respectively located within a plurality of cuvettes includes aholder to hold the plurality of cuvettes, a traveler mechanismconfigured to translate upwardly towards the plurality of cuvettes heldby the holder and position a plurality of magnets adjacent to theplurality of cuvettes so that each cuvette of the plurality of cuvetteshas a first magnet of the plurality of magnets adjacent to a first sideand a second magnet of the plurality of magnets adjacent to an oppositesecond side, thereby suspending magnetic particles located within eachof the plurality of cuvettes, and a wash system configured to translatedownwardly towards the plurality of cuvettes held by the holder so as toposition a probe within each of the plurality of cuvettes while theplurality of magnets suspend the magnetic particles located within eachof the plurality of cuvettes.

In another embodiment, the system includes a rotor, the rotor includesthe holder, and the rotor is configured to rotate the plurality ofcuvettes about an axis to position the cuvettes over the travelersystem.

In another embodiment, the axis of rotation of the rotor is a verticalaxis, and the traveler mechanism is configured to translate upwardlyparallel to the vertical axis.

In another embodiment, the traveler mechanism includes a guide rail anda sliding device, and the sliding device translates along the guide railto position the plurality of magnets adjacent to the plurality ofcuvettes.

In another general embodiment, a method of washing a plurality of fluidsamples respectively located within a plurality of cuvettes includesadding magnetic particles to the plurality of cuvettes, rotating theplurality of cuvettes over a plurality of magnets, raising the pluralityof magnets so that each cuvette of the plurality of cuvettes has a firstmagnet of the plurality of magnets adjacent to a first side and a secondmagnet of the plurality of magnets adjacent to an opposite second side,suspending the magnetic particles in the plurality of cuvettes with theplurality of magnets, lowering a plurality of probes so that eachcuvette of the plurality of cuvettes has a probe of the plurality ofprobes located therein, and aspirating fluid from each cuvette of theplurality of cuvettes with a respective probe.

In another embodiment, raising the magnets includes positioning a magnethaving a first polarity adjacent to the first side and a magnet havingan opposite second polarity adjacent to the second side.

In another embodiment, the method includes raising the plurality ofprobes away from the cuvettes and detecting if one or more of the probesbecomes misaligned.

In another embodiment, the method includes locking the cuvettes into arotor with a removeable lid.

In another embodiment, the method includes raising the plurality ofmagnets and lowering the plurality of probes in directions parallel to arotational axis of the cuvettes.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the present disclosure will now be explained in furtherdetail by way of example only with reference to the accompanyingfigures, in which:

FIG. 1 is a top plan view of an embodiment of a reaction rotor accordingto the present disclosure;

FIG. 2 is a top perspective view of an embodiment of a magnetic travelersystem according to the present disclosure located underneath thereaction rotor of FIG. 1 ;

FIG. 3 is a side cross-sectional view of an embodiment of a magnetictraveler system according to the present disclosure;

FIG. 4 is a side cross-sectional view of an embodiment of a magnetictraveler system according to the present disclosure;

FIG. 5 is a side cross-sectional view of an embodiment of a magnetictraveler system according to the present disclosure working inconjunction with an embodiment of a multi-rinse system according to thepresent disclosure;

FIG. 6 is a side cross-sectional view of an embodiment of a magnetictraveler system according to the present disclosure working inconjunction with an embodiment of a multi-rinse system according to thepresent disclosure;

FIG. 7 is a side cross-sectional view of an embodiment of a magnetictraveler system according to the present disclosure working inconjunction with an embodiment of a multi-rinse system according to thepresent disclosure;

FIG. 8 is a top perspective view of an embodiment of a magnetic travelersystem according to the present disclosure;

FIG. 9 is a side elevational view of an embodiment of a lid mechanismaccording to the present disclosure;

FIG. 10 is a side elevational view of an embodiment of a lid mechanismaccording to the present disclosure;

FIG. 11 is a side elevational view of an embodiment of a lid mechanismaccording to the present disclosure; and

FIG. 12 is a top plan view of an embodiment of a lid mechanism accordingto the present disclosure.

DETAILED DESCRIPTION

Before describing in detail the illustrative system and method of thepresent disclosure, it should be understood and appreciated herein thatas a way of minimizing background signals caused by interferingsubstances present in specimens and reagents, immunoassays generallyrequire that one or more separation phases be carried out in a reactioncuvette. To facilitate the separation or washing process, a variety oftechniques can be used, including, but not limited to, well coatingtechniques, bead coating techniques, or the use of paramagneticparticles. According to certain aspects of the present disclosure, thesystem utilizes common paramagnetic particles, including, but notlimited to, magnetic beads or microparticles. When paramagneticparticles are used as separation media, the paramagnetic particles arepulled to the wall of the cuvette by magnets during the washing processand then all of the liquid is aspirated.

In the beginning of the process, the paramagnetic particles are coatedwith a capture reagent that will eventually bind analyte molecules ofinterest in the patient's blood sample. In accordance with certainaspects of the present teachings, the biotinylated capture reagent canexist as an amalgam or mixture (i.e., capture reagents from a similarcategory but from different genus species). As those of skill in the artwill understand and appreciate herein, numerous capture reagents areavailable and can be used in accordance with the present teachings,including those available for license from the FDA, such as Mixed VespidVenom Protein (mixed yellow jacket, yellow hornet, and white facedhornet). It should be understood herein that the amount and volume ofeach of the individual capture reagents used in accordance with thepresent disclosure depends on the potency (i.e. the ability to produce adetectable response). In accordance with certain aspects of the presentdisclosure, a capture reagent that can be used for performing adiagnostic immunoassay is comprised of Biotin-pAb or Biotin-allergens,10 mM sodium phosphate, pH 7.4, 0.9% NaCl, 0.05% Tween-20, 1% (w/v)human serum albumin, 1% (v/v) ProClin 950, up to 5% (v/v) glycerol. Inaccordance with still other aspects of the present disclosure, anothercapture reagent that can be used for performing a diagnostic immunoassayis comprised of Biotin-Ags, 10 mM sodium phosphate, pH 7.4, 0.9% (w/v)NaCl, 0.05% Tween-20, 1% (w/v) bovine serum albumin, 1% (v/v) ProClin950, 1% protease inhibitor cocktail, 0.1 mM DTT, 25% (up to 30%) (v/v)glycerol.

After the capture reagents bind to the paramagnetic particles and thecuvettes undergo a washing process, the patient sample, and optionally adiluent if needed, is added to the particles in the cuvettes andincubated. This allows analytes of interest in a patient's blood samplebind to the capture reagent that has in turn been bound to the surfaceof a paramagnetic particle. In accordance with one specific illustrativeaspect of the present disclosure, the reaction diluent (sample diluent)is comprised of 10 mM sodium phosphate, pH 7.4, 500 mM NaCl, 0.02%Tween-20, 1% (w/v) human serum albumin, 1% (v/v) human IgG, 1% (v/v)ProClin 950, 0.005% Antifoam-B v/v, 2% (w/v) PEG 6,000. In accordancewith yet another specific illustrative aspect of the present disclosure,the reaction diluent (sample diluent) is comprised of 10 mM sodiumphosphate, pH 7.4, 500 mM NaCl, 0.02% Tween-20, 25% (w/v) human serumalbumin, 1% (v/v) ProClin 950. In accordance with these illustrativeembodiments, it should be understood herein that the high percentage ofHSA (25%) functions in part to increase the viscosity of the reactionmedium in order to retain beads in suspension during the incubationstep. In addition, high HSA also reduces non-specific binding duringthis incubation, and improves relative light unit (RLU) linearity upondilution of the patient sample.

After the patient sample incubation period, another washing process isperformed to remove any excess or unbound sample, and then a conjugateand a luminescent label are added to the cuvette. When added to thecuvette, it can be expected that some portion of the conjugate will bindto the capture reagent/sample complex on the paramagnetic particlesafter an incubation period. The particles then undergo another washprocess to remove any unbound conjugate, and then the luminescent labelis added to the cuvette and incubated for a short period of time toallow the chemiluminescent glow reaction to reach equilibrium. Afterequilibrium is reached, luminescence and fluorescence readings of thesample can be taken.

In accordance with the above-described process, the present disclosureprovides an apparatus and method for performing the wash steps after anyone of the capture reagent, patient sample, luminescent label andconjugate are added to a plurality of cuvettes and allowed to bind withparamagnetic particles within the cuvettes. That is, the presentdisclosure provides an efficient system and method for performing one ormore wash steps within the cuvettes while the paramagnetic particles arelocalized.

FIGS. 1 to 8 illustrate a system for washing a plurality of cuvettes 18.In an embodiment, the system includes a reaction rotor 10, a magnetictraveler mechanism 30 and a multi-wash mechanism 60, and can furtherinclude a lid mechanism 100. Although these elements of the system areshown separately in the various drawings, it will be understood by thefollowing disclosure that each element from the drawings can operateindividually or in combination with each other element in the drawings,and that the combination of some or all of these elements working inconjunction with each other provides an advantageous system and methodfor suspending paramagnetic particles within a plurality of cuvettes andperforming a number of washing steps.

FIG. 1 illustrates a top view of an embodiment of a reaction rotor 10according to the present disclosure. In use, reaction rotor 10 rotates aplurality of cuvettes 18 and creates an environment that allowsparamagnetic particles to be suspended within the cuvettes 18 for anumber of washing steps. Although not shown in FIG. 1 , the magnetictraveler mechanism 30 is located below the reaction rotor 10 in apreferred embodiment, and the multi-wash mechanism 60 is located abovethe reaction rotor 10 in a preferred embodiment. The interaction ofthese elements with reaction rotor 10 is described in more detail below.

As illustrated, reaction rotor 10 includes a top surface 12 that has aplurality of sections 14. Each section 14 includes a plurality ofapertures 16. In the illustrated embodiment, there are twenty sections14, and each section 14 includes ten apertures 16, but those of ordinaryskill in the art will understand that any number of sections 14 andapertures 16 can be used.

Each aperture 16 is configured to receive a cuvette 18 (FIGS. 2 to 7 ),so in the illustrated embodiment, each section 14 is configured toreceive ten cuvettes 18. The cuvettes 18 placed in the apertures 16within each section 14 can be connected to each other, can be separatecuvettes 18 that are each individually loaded into the apertures 16, orcan be made a permanent part of reaction rotor 10. In an embodiment, acuvette rack 17 including a plurality of connected cuvettes 18 can beinserted into one or more of the sections 14 so that each connectedcuvette 18 is received by a corresponding aperture 16 in the section 14.

As illustrated in FIG. 1 , each section 16 is angled from the outerdiameter of the reaction rotor 10 to an inner diameter of the reactionrotor 10, and the plurality of apertures 18 within each section 14 forman arc from the end of each section 14 located at the outer diameter ofthe reaction rotor 10 to the opposite end of each section 14 at theinner diameter of the reaction rotor 10. As explained in more detailbelow, the arc of the cuvettes is advantageous because it eliminatesmagnetic cross-talk between magnets 40, 41 that operate in conjunctionwith reaction rotor 10. The arc of the cuvettes also allows variousrotating pipettes to access each of the cuvettes in the arc.

The cuvettes 18 that are loaded into the apertures 16 of reaction rotor10 are typically initially empty, but can also be loaded into theapertures 16 already containing paramagnetic particles. If emptycuvettes are loaded into the apertures 16, then a pipette (not shown)can transfer paramagnetic particles to the reaction rotor 10 and injectthe paramagnetic particles into one or more of the cuvettes 18 locatedwithin the apertures 16. Once the paramagnetic particles are located inthe cuvettes, a capture reagent can be injected into each cuvette 18 bythe same or a different pipette, or by multi-wash mechanism 60 describedin more detail below. That is, one or more pipettes can aspirate adesired quantity of paramagnetic particles and transfer the aspiratedquantity to the reaction rotor 10, where the paramagnetic particles canbe injected by the pipette into one or more of the cuvettes 18 locatedwithin the apertures 16. The one or more pipettes can then aspirate adesired quantity of a capture reagent and transfer the aspiratedquantity to the reaction rotor 10, where the capture reagent can then bemixed with the paramagnetic particles in the cuvettes 18. In anembodiment, the pipette that injects the paramagnetic particles, capturereagent or other fluid into a cuvette 18 can vibrate within the cuvetteto mix the contents of the cuvette during injection or aspiration.

Once the paramagnetic particles and the capture reagent have been addedto one or more of the cuvettes, the capture reagent is allowed to bindto the paramagnetic particles during an incubation period. Typically,the incubation period is about five minutes. After the incubationperiod, the excess capture reagent that does not bind to theparamagnetic particles must be removed from the cuvettes using themagnetic traveler mechanism 30 and multi-wash mechanism 60 inconjunction with reaction rotor 10. As described in more detail below,magnetic traveler mechanism 30 is configured to localize theparamagnetic particles within each of the cuvettes in a single section14 so that multi-wash mechanism 60 can wash the cuvettes to removeexcess capture reagent. Magnetic traveler mechanism 30 and multi-washmechanism 60 work in conjunction with reaction rotor 10 to performadditional washing steps after the addition and incubation of otherfluids, such as the patient sample, luminescent label and conjugate.

FIG. 2 illustrates a magnetic traveler mechanism 30 located underneathreaction rotor 10. In the illustrated embodiment, magnetic travelermechanism 30 includes a guide rail 32 and a sliding device 34. In theillustrated embodiment, guide rail 32 is attached to a lower arm 33 thatis attached to a lower surface of reaction rotor 10, and sliding device34 is moveably attached to guide rail 32. In use, sliding device 34slides along guide rail 32 so as to vertically translate a plurality ofmagnets 40, 41 both towards and away from reaction rotor 10 in anup/down direction. Sliding device 34 is further configured to lock intoplace underneath reaction rotor 10 so as to locate pairs of magnets 40,41 on opposite sides of each cuvette 18 located in the reaction rotor 10to localized the paramagnetic particles located within the cuvettes 18.Sliding device 34 can then travel back away from the cuvettes 18 whenthe paramagnetic particles do not need to be localized.

FIG. 3 illustrates sliding device 34 positioned in a nonsuspension statebelow a cuvette rack 17. The cuvette rack 17 includes a plurality ofcuvettes 18 that are positioned within a plurality of adjacent apertures18 within a single section 14 of reaction rotor 10 (shown in brokenlines in FIG. 3 ). The cuvette rack 17 includes a plurality ofconnections 19 which hold the cuvettes 18 together so that the cuvettes18 can be inserted into corresponding adjacent apertures 16 of a singlesection 14 in one motion. Alternatively, each cuvette 18 can be separatefrom one or more of the adjacent cuvettes 18 and can be separatelyinserted into a corresponding aperture 16 of section 14. Although notshown from this perspective, the cuvettes 18 in FIG. 3 are positioned inthe arc of the apertures 16 shown in FIG. 1 .

Sliding device 34 includes a magnet holder 36 with a plurality ofmagnets 40, 41. In the illustrated embodiment, there are ten cuvettes 18and eleven magnets 40, 41 so that each cuvette 18 is surrounded onopposite sides by a pair of magnets. In other words, each cuvette 18 hasa magnet 40, 41 on each side when the magnets 40, 41 are raised up tothe cuvettes 18 by the sliding device 34. In an embodiment, the magnets40, 41 can include a plurality of first magnets 40 and a plurality ofsecond magnets 41, wherein the first magnets 40 each have a polaritythat is opposite the polarity of the second magnets 41. The firstmagnets 40 and the second magnets 41 are positioned in the magnet holder36 so that they alternate from a first side 38 of the magnet holder 36to a second side 39 of the magnet holder 36. This alternatingconfiguration allows each cuvette 18 to have a first magnet 40 on afirst side 21 and a second magnet 41 on an opposite second side 22 whenthe magnets 40, 41 are raised up to the cuvettes. In alternativeembodiments, adjacent magnets can have the same charge or can haveopposite polarity sides so that each cuvette 18 is still surrounded byopposite polarities.

FIG. 4 illustrates sliding device 34 positioned in a suspension stateafter sliding device 34 has been translated upwards towards the cuvettes18 located in the apertures 16 of reaction rotor 10. As illustrated, theplurality of magnets 40, 41 have been raised to the plurality ofcuvettes 18 so that each cuvette 18 has a first magnet 40 adjacent to afirst side 21 and a second magnet 41 adjacent to an opposite second side22. This alternating of first magnets 40 and second magnets 41 creates amagnetic field across each cuvette 18 which can suspend paramagneticparticles in the cuvettes 18 while the cuvettes 18 are washed bymulti-wash mechanism 60.

As described above, the cuvettes 18 in FIG. 4 are each first filled withparamagnetic particles and a capture reagent while the sliding device 34is in the nonsuspension state (FIG. 3 ). The capture reagent then bindsto the paramagnetic particles within each cuvette during an incubationperiod. The capture reagent can bind to the paramagnetic particles byany chemical bond or physical attraction. Chemical bonds can includecovalent or ionic bonds. Physical attraction can be through, forexample, Van der Waals forces, hydrogen bonding, or the like. In oneembodiment, an immunological system can be used in conjunction with thebeads. For example, the paramagnetic beads can be coated withstrepavadin which can bind a capture reagent that is specific for aparticular human antigen. Strong forces between the solid phaseimmunological system and the magnetic beads can prevent wash-away whenthe beads are attracted to the magnetic field and washed.

After the capture reagent binds to the paramagnetic particles, it isdesirable to remove excess unbound capture reagent from the cuvettes.For this purpose, the sliding device 34 is raised to the suspensionstate illustrated in FIG. 4 . As described above, the suspension stateplaces the magnets 40, 41 so that each cuvette 18 is surrounded onopposite sides by a first magnet 40 and a second magnet 41, whichcreates a magnetic field across each cuvette 18. The magnetic fieldlocalizes within each cuvette 18 the paramagnetic particles along withthe capture reagent that is bound to the paramagnetic particles.Although not shown from this perspective, the magnets 40, 41 arepositioned in an arc corresponding to the arc of the cuvettes 18, as canbe seen in FIG. 2 . The arc of the magnets 40, 41 is advantageous inthis respect because the arc helps eliminate magnetic cross-talk betweenmagnets.

The sliding device 34 includes a locking mechanism 46 (FIG. 2 ) thatlocks the sliding device 34 into the suspension state when it isdesirable to localize the paramagnetic particles located in the cuvettes18. In the illustrated embodiment, the locking mechanism 46 includes twoarms 47 that surround a bulbous portion 51 of a corresponding protrusion50 located on the underside of the reaction rotor 10. In an embodiment,the arms 47 of locking mechanism 46 can snap-fit around protrusion 50 tolock sliding device 34 into the suspension state, and sliding device 34or reaction rotor 10 can further include a release button to release thearms 47 of locking mechanism 46 from protrusion 50 when the slidingdevice 34 needs to be dropped to the nonsuspension state. Those ofordinary skill in the art will also understand that the positioning oflocking mechanism 46 and protrusion 50 can be reversed so that lockingmechanism 46 is located on an underside of the reaction rotor andprotrusion 50 is located on sliding device 34. In an embodiment, themagnetic traveler mechanism 30 can be operably connected to a computerto automate the raising, lowering and locking of the magnets 40, 41 inthe suspension state.

In an embodiment, sliding device 34 further includes a base portion 37separate from the magnet holder 36. As illustrated in FIG. 2 , lockingmechanism 46 is located on base portion 37, and magnet holder 36 isattached to base portion 37 by one or more rods 52. In the illustratedembodiment, the rods are fixed to magnet holder 36 and are slideablyattached to base portion 37 so that magnet holder 36 can verticallytranslate with respect to base portion 37. This vertical translationassists in positioning the magnets 40, 41 around the cuvettes 18 whenthe sliding device 34 is in the suspension state. In this embodiment,the movement of base portion 37 towards magnet holder 36 compresses oneor more springs 53 located between base portion 37 and magnet holder 36once magnet holder 36 reaches its uppermost position. As the springs 53are compressed, the springs 53 apply a force against both the baseportion 37 and magnet holder 36 which pushes the magnet holder 36 to itsuppermost position when the base portion 37 is locked into the reactionrotor 10 via locking mechanism 46.

Once the paramagnetic particles have been localized within each cuvette18 by the magnets 40, 41, a washing step can be performed. In thisexample, the washing step is used to remove excess capture reagent, butwashing steps are also used to remove other fluids from the cuvettes,such as a patient sample, conjugate sample or luminescent label. Duringa washing step, a rinse buffer is injected into the cuvettes and thenaspirated from the cuvettes and disposed of.

FIG. 5 illustrates a multi-wash mechanism 60 located above cuvette rack17, which is positioned within reaction rotor 10 (shown in brokenlines), as a plurality of magnets 40, 41 from magnetic travelermechanism 30 localize the paramagnetic particles within the cuvettes 18of cuvette rack 17. In FIG. 5 , multi-wash mechanism 60 is shown in araised state. As illustrated, multi-wash mechanism 60 includes a base 62with a plurality of probes 64 extending therefrom. In the illustratedembodiment, multi-wash mechanism 60 includes ten probes 64 whichcorrespond to each of the ten cuvettes 18 located on cuvette rack 17,but those of ordinary skill in the art will understand that more or lessprobes 64 can be used. One advantage of the present disclosure is thatnumber of cuvettes 18, magnets 40, 41 and probes 64 correspond to oneanother so that the cuvettes 18 within each portion 14 of reaction rotor10 can simultaneously have their respective paramagnetic particleslocalized by the magnets 40, 41 of magnetic traveler mechanism 30 whilebeing washed by multi-wash mechanism 60. Only a single magnetic travelermechanism 30 and a corresponding single multi-wash mechanism 60 areneeded for this configuration because reaction rotor 10 can rotate eachportion 14 of cuvettes 18 over the magnetic traveler mechanism 30 andbeneath the multi-wash mechanism 60.

In an embodiment, multi-wash mechanism 60 includes a probe positioningsensor 70. In the illustrated embodiment, probe positioning sensor 70includes a light emitter 72 and a light receiver 74. Light emitter 72transmits a beam of light 76 to light receiver 74. When light receiver74 receives the light 76 from light emitter 72, the system recognizesthat the probes 64 are located in their initial position. When the light76 is not sensed by light receiver 74, the system alerts a user that oneof the probes 64 has not returned to its initial position. In FIG. 5 ,the system recognizes that the probes 64 are all located in theirinitial position and are ready to be lowered into the correspondingcuvettes 18.

FIG. 6 shows the multi-wash mechanism 60 in a washing state after theprobes 64 have been lowered into corresponding cuvettes 18. Although notshown from this perspective, the probes 64 are positioned in an arccorresponding to the arc of the cuvettes 18. In the illustratedembodiment, the probes are lowered until they contact a bottom surface24 of each cuvette 18. The probes 64 are vertically moveable withrespect to base 62, so the probes 64 each shift upwards with respect tobase 62 as base 62 continues to move downward after the tip 67 of eachprobe comes into contact with the bottom surface 24 of each cuvette 18.This configuration ensures that the tip 67 of each probe 64 extends allthe way to the bottom surface 24 of each cuvette 18. The tapered bottomsurface 24 of the cuvettes 18 also ensures that the tip 67 of the probe64 can aspirate all of the liquid in each cuvette 18. In the illustratedembodiment, the probes 64 have each shifted upwards a distance D withrespect to base 64, meaning that the base 62 continued to movedownwardly a distance D after the tips 67 of the cuvettes contacted therespective bottom surfaces 24 of the cuvettes 18. In the washing stateshown in FIG. 6 , an upper end 68 of each of the probes 64 lies in thelight path between light emitter 72 and light receiver 74, so that nolight is received by light receiver 74. Upper end 68 can include aportion of the probe 64 itself or any structure attached to the probe 64that is capable of blocking light 76 that is emitted from light emitter72. In an embodiment, light emitter 72 and light receiver 74 can belocated in other positions than shown in FIG. 6 , and different shapedupper ends 68 operably attached to each of the probes 64 can be used toblock the different light path caused by the different positioning.

FIG. 7 shows the multi-wash mechanism 60 after it has been lifted backto its initial raised state. As illustrated, one of the probes 64 hasnot returned to its initial position and remains shifted with respect tobase 62 so that its upper end 68 lies in the light path from lightemitter 72. Since light receiver 74 is not receiving any light 76 fromlight receiver 72, the system can issue an alert that at least one ofthe probes 64 has not returned to its initial position, and the systemor a user can fix the positioning of the probes 64 before another washstep occurs.

As illustrated in FIGS. 5 to 7 , each probe 64 has a trident-shape thatincludes a first portion 65 and two second portions 66. The firstportion 65 is longer than the second portions 66 and extends to thebottom surface 24 of a corresponding cuvette 18 when the multi-washmechanism 60 is in its washing configuration. When the probe 64 islocated within a cuvette 18, first portion 65 is used to aspirate thecuvette 18. The second portions 66 are shorter than the first portion 65and serve to push out fluid while the probe 64 is located within thecuvette 18. The second portions can also advantageously be rotationallyangled outwardly with respect to the radius of the cuvette to push fluidin a circular motion (e.g., clockwise or counterclockwise around thecuvette's central axis) and create a cyclone effect within the cuvette.

In an embodiment, the second portions 66 deliver washing solution to thecuvettes. The delivery of the washing solution via second portions 66agitates the contents of the cuvette to wash away the capture reagent orother sample that is not sufficiently bound to the paramagnetic beads.After or during agitation, the washing solution can be aspirated byfirst portion 65. In an alternative embodiment, each probe 64 caninclude only one or more than two second portions 66. By using both thefirst portion 65 and at least one second portion 66, the multi-washmechanism 60 can simultaneously inject fluid into and aspirate fluidfrom each cuvette 18 in a single wash step. In an embodiment, the probes64 can vibrate within the cuvette 18 to mix the contents of the cuvetteduring injection or aspiration.

FIG. 8 illustrates a side perspective view of multi-wash mechanism 60with elements that have been omitted from FIGS. 5 to 7 for simplicity.It should be understood that every element in FIG. 8 could also be shownin FIGS. 5 to 7 if necessary. As illustrated, base 62 is attached to afirst end 82 of arm 80. A second end 84 of arm 80 is attached to a rod86 that rotates about a vertical axis at its base 87. The rotation ofrod 86 rotates arm 80 and base 62 so that the probes 64 can be movedbetween a rinse station 88 and each portion 14 of reaction rotor 10. Rod86 can also be vertically raised or lowered, so as to raise and lowerthe probes 64 into or out of the cuvettes 18 or rinse station 88. Rinsestation 88 can rinse the probes 64 of multi-wash mechanism 60 when theprobes 64 are lowered into apertures in the rinse station 88.

As illustrated, a plurality of tubes 90 are connected to the probes 64.The tubes 90 run from fluid supplies (not shown, located below coupling92) to the probes 64 at base 62. Each probe 64 can be connected to asingle tube 90 or to multiple tubes 90. In an embodiment, each probe 64is connected to at least two tubes 90 so that each probe 64 cansimultaneously inject fluid through at least one second portion 66 andaspirate fluid through at least one first portion 65. In such anembodiment, each probe 64 is connected to at least one tube 90 forinjection and at least one tube 90 for aspiration. Each second portion66 can also be attached to a separate tube 90, for example, so that eachprobe with one first portion 65 and two second portions 66 is attachedtwo three tubes 90 (one tube 90 for the first portion 65, and a tube 90for each second portion 66). In another embodiment, each probe 64 isconnected to one tube 90 and can alternate between injecting andaspirating fluid through the tube 90. The tubes 90 can also each includecheck valves 94 to prevent leakage as fluid is either injected into oraspirated from the cuvettes 18. In an embodiment, the check valves 94are located proximal to the upper end 68 of the probes 64 to prevent theprobes from dripping as fluid is dispensed. The tubes 90 can also beoperatively connected to a heater to control the temperature of thefluid injected from the probes 64.

The fluid supplies connected to the plurality of tubes 90 just belowcoupling 92 can include, for example, a wash buffer. Distilled water canalso be run through the probes to flush them out. In an embodiment, thefluid supplies are positioned on load cells so that the amount of fluidinto the cuvettes can be determined based on the difference between theoriginal weight of the fluid supply and the weight of the fluid supplyafter injection. Drain bags can also be positioned on load cells to keeptrack of the amount of fluid aspirated from the cuvettes 18 during awash.

The method according to the present disclosure accordingly begins, asdescribed above, by adding paramagnetic particles and a capture reagentto each of the cuvettes 18 in a section 14 of reaction rotor 10. Afterthe capture reagent binds to the paramagnetic particles within eachcuvette 18, magnetic traveler mechanism 30 can be used to localize theparamagnetic particles while multi-wash mechanism 60 washes excessunbound capture reagent from the cuvettes 18. This step constitutes thefirst wash step in a multi-wash method.

Once excess capture reagent has been removed from the cuvettes 18,reaction rotor 10 can rotate the cuvettes 18 so that a patient samplecan be injected into the cuvettes 18 to bind with the paramagneticparticles during another incubation period due to the presence of thecapture reagent already bound to the paramagnetic particles. Excesspatient sample must then be washed from the cuvettes 18 by rotating thecuvettes 18 over the magnetic traveler mechanism 30 and localizing theparamagnetic particles while multi-wash mechanism 60 washes excessunbound patient sample from the cuvettes. To localize and wash thepatient sample, magnetic traveler mechanism 30 and multi-wash mechanism60 operate as described above with respect to the capture reagent. In anembodiment, three separate washes are performed on each cuvette 18 afterthe patient incubation period in which the patient sample binds to theparamagnetic particles.

After the patient sample washes, reaction rotor 10 can rotate thecuvettes 18 so that a conjugate sample can be injected into the cuvettesto bind with the paramagnetic particles during another incubationperiod. Excess conjugate sample must then be washed from the cuvettes 18by rotating the cuvettes 18 over the magnetic traveler mechanism 30 andlocalizing the paramagnetic particles while multi-wash mechanism 60washes excess unbound conjugate from the cuvettes. To localize and washthe conjugate, magnetic traveler mechanism 30 and multi-wash mechanism60 operate as described above with respect to the capture reagent. In anembodiment, four separate washes are performed on each cuvette 18 afterthe incubation period in which the conjugate binds to the paramagneticparticles. One or more washes can also be performed after the additionand incubation of the luminescent label.

Reaction rotor 10, magnetic traveler mechanism 30 and multi-washmechanism 60 can therefore operate together to perform a number ofwashing steps for a number of different samples that bind to theparamagnetic particles. Reaction rotor 10 is positioned with respect tomagnetic traveler mechanism 30 and multi-wash mechanism 60 so that awashing step can be performed on one section 14 of reaction rotor 10while a sample is added to the cuvettes 18 in another section 14.Reaction rotor 10 can then continue to rotate so that the cuvettes 18 inthe other section 14 can be washed. By operating in this manner,reaction rotor 10, magnetic traveler mechanism 30 and multi-washmechanism 60 provide an efficient system for washing the cuvettes 18.

FIGS. 9 to 12 illustrate a lid mechanism 100 according to the presentdisclosure. Lid mechanism 100 can operate in conjunction with reactionrotor 10, magnetic traveler mechanism 30 and multi-wash mechanism 60 sothat the cuvettes 18 placed on reaction rotor 10 are held stationary inthe correct position while reaction rotor 10 rotates the cuvettes 18,while magnetic traveler system 30 raises the magnets 40, 41 to thecuvettes, and while multi-wash mechanism 60 performs one or more washingsteps.

FIG. 9 shows lid mechanism 100 with a lid 102 that is hinged to reactionrotor 10 in a raised configuration. In the raised configuration, one ormore cuvettes 18 can be loaded into reaction rotor 10. Once loaded, lid102 is lowered as illustrated in FIG. 10 . As lid 102 is lowered, lid102 can slightly compress the cuvettes 18 against reaction rotor 10 sothat the cuvettes 18 remain in the correct position even if nudged bymagnetic traveler mechanism 30 or multi-wash mechanism 60 as they areraised and lowered towards and away from the cuvettes 18. As understoodfrom the discussion above, an advantage of the present disclosure isthat the reaction rotor 10, magnetic traveler mechanism 30 andmulti-wash mechanism 60 are all positioned to work together so that thecuvettes 18 are rotated into a position where multiple cuvettes 18 canhave their paramagnetic particles localized during one or more washingsteps. Ensuring that the cuvettes 18 do not shift during the process isimportant to the overall functionality of the system.

As illustrated in FIGS. 9 to 12 , lid 102 has an attachment mechanism104 that holds lid 102 against the cuvettes 18 and reaction rotor 10 andprevents lid 102 from being raised during use of reaction rotor 10. Inthe illustrated embodiment, attachment mechanism 104 includes a tab 106that projects outwardly from lid 102. As illustrated in FIG. 10 , tab106 is positioned adjacent to a corresponding arm 108 on reaction rotor10 when lid 102 is lowered onto the cuvettes 18. Lid 102 can then betranslated to the side (to the left in FIG. 11 ) so that arm 108receives tab 106 and holds lid 102 against reaction rotor 10 until lid102 is then translated back in the other direction. As illustrated inFIG. 12 , lid 102 includes an opening on its upper surface that allowsthe probes 64 of multi-wash mechanism 60 to access each cuvette 18. Thetop surface 12 of reaction rotor 10 can also be raised or lowered toensure that tab 106 and arm 108 fit together.

It should be understood that various changes and modifications to thepresently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications can be madewithout departing from the spirit and scope of the present subjectmatter and without diminishing its intended advantages. It is thereforeintended that such changes and modifications be covered by the appendedclaims.

Unless otherwise indicated, all numbers expressing quantities ofingredients, properties such as molecular weight, reaction conditions,and so forth used in the specification and claims are to be understoodas being modified in all instances by the term “about.” Accordingly,unless indicated to the contrary, the numerical parameters set forth inthe following specification and attached claims are approximations thatmay vary depending upon the desired properties sought to be obtained bythe present disclosure. At the very least, and not as an attempt tolimit the application of the doctrine of equivalents to the scope of theclaims, each numerical parameter should at least be construed in lightof the number of reported significant digits and by applying ordinaryrounding techniques. Notwithstanding that the numerical ranges andparameters setting forth the broad scope of the disclosure areapproximations, the numerical values set forth in the specific examplesare reported as precisely as possible. Any numerical value, however,inherently contains certain errors necessarily resulting from thestandard deviation found in their respective testing measurements.

The terms “a” and “an” and “the” and similar referents used in thecontext of the disclosure (especially in the context of the followingclaims) are to be construed to cover both the singular and the plural,unless otherwise indicated herein or clearly contradicted by context.Recitation of ranges of values herein is merely intended to serve as ashorthand method of referring individually to each separate valuefalling within the range. Unless otherwise indicated herein, eachindividual value is incorporated into the specification as if it wereindividually recited herein. All methods described herein can beperformed in any suitable order unless otherwise indicated herein orotherwise clearly contradicted by context. The use of any and allexamples, or exemplary language (e.g. “such as”) provided herein isintended merely to better illuminate the disclosure and does not pose alimitation on the scope of the disclosure otherwise claimed. No languagein the specification should be construed as indicating any non-claimedelement essential to the practice of the disclosure.

The use of the term “or” in the claims is used to mean “and/or” unlessexplicitly indicated to refer to alternatives only or the alternativesare mutually exclusive, although the disclosure supports a definitionthat refers to only alternatives and “and/or.”

Groupings of alternative elements or embodiments of the disclosuredisclosed herein are not to be construed as limitations. Each groupmember may be referred to and claimed individually or in any combinationwith other members of the group or other elements found herein. It isanticipated that one or more members of a group may be included in, ordeleted from, a group for reasons of convenience and/or patentability.When any such inclusion or deletion occurs, the specification is hereindeemed to contain the group as modified thus fulfilling the writtendescription of all Markush groups used in the appended claims.

Preferred embodiments of the disclosure are described herein, includingthe best mode known to the inventors for carrying out the disclosure. Ofcourse, variations on those preferred embodiments will become apparentto those of ordinary skill in the art upon reading the foregoingdescription. The inventor expects those of ordinary skill in the art toemploy such variations as appropriate, and the inventors intend for thedisclosure to be practiced otherwise than specifically described herein.Accordingly, this disclosure includes all modifications and equivalentsof the subject matter recited in the claims appended hereto as permittedby applicable law. Moreover, any combination of the above-describedelements in all possible variations thereof is encompassed by thedisclosure unless otherwise indicated herein or otherwise clearlycontradicted by context.

Specific embodiments disclosed herein may be further limited in theclaims using consisting of or consisting essentially of language. Whenused in the claims, whether as filed or added per amendment, thetransition term “consisting of” excludes any element, step, oringredient not specified in the claims. The transition term “consistingessentially of” limits the scope of a claim to the specified materialsor steps and those that do not materially affect the basic and novelcharacteristic(s). Embodiments of the disclosure so claimed areinherently or expressly described and enabled herein.

Further, it is to be understood that the embodiments of the disclosuredisclosed herein are illustrative of the principles of the presentdisclosure. Other modifications that may be employed are within thescope of the disclosure. Thus, by way of example, but not of limitation,alternative configurations of the present disclosure may be utilized inaccordance with the teachings herein. Accordingly, the presentdisclosure is not limited to that precisely as shown and described.

ADDITIONAL ASPECTS OF THE PRESENT DISCLOSURE

Aspects of the subject matter described herein may be useful alone or incombination with any one or more of the other aspect described herein.Without limiting the foregoing description, in a first aspect of thepresent disclosure, a system for washing a plurality of fluid samplesrespectively located within a plurality of cuvettes includes a rotorconfigured to rotate the plurality of cuvettes about an axis, a travelermechanism located beneath the rotor, the traveler mechanism configuredto move a plurality of magnets parallel to the axis of rotation of therotor to position the plurality of magnets so that each cuvette of theplurality of cuvettes is located adjacent to at least one magnet of theplurality of magnets, and a wash system located above the rotor, thewash system configured to at least one of inject fluid into or aspiratefluid from the plurality of the cuvettes, while the plurality of magnetssuspend magnetic particles located within each of the plurality ofcuvettes.

In accordance with a second aspect of the present disclosure, which maybe used in combination with any other aspect or combination of aspectslisted herein, the axis of rotation of the rotor is a vertical axis.

In accordance with a third aspect of the present disclosure, which maybe used in combination with any other aspect or combination of aspectslisted herein, the wash system is configured to inject fluid into andaspirate fluid from the plurality of the cuvettes.

In accordance with a fourth aspect of the present disclosure, which maybe used in combination with any other aspect or combination of aspectslisted herein, the plurality of magnets includes a plurality of firstmagnets with a first polarity and a plurality of second magnets with anopposite second polarity.

In accordance with a fifth aspect of the present disclosure, which maybe used in combination with any other aspect or combination of aspectslisted herein, the traveler system is configured to position theplurality of magnets so that each of the plurality of cuvettes has afirst magnet on a first side and a second magnet on an opposite secondside.

In accordance with a sixth aspect of the present disclosure, which maybe used in combination with any other aspect or combination of aspectslisted herein, the wash system includes a plurality of probes configuredto at least one of inject fluid into or aspirate fluid from theplurality of the cuvettes.

In accordance with a seventh aspect of the present disclosure, which maybe used in combination with any other aspect or combination of aspectslisted herein, the probes each include a first portion to aspirate fluidfrom a respective cuvette and a second portion to inject fluid into therespective cuvette.

In accordance with an eighth aspect of the present disclosure, which maybe used in combination with any other aspect or combination of aspectslisted herein, the wash system includes a probe positioning sensorconfigured to determine if at least one of the probes is misaligned.

In accordance with a ninth aspect of the present disclosure, which maybe used in combination with any other aspect or combination of aspectslisted herein, the traveler mechanism includes a guide rail and asliding device, and the sliding device translates along the guide railto position the plurality of magnets so that each cuvette of theplurality of cuvettes is located adjacent to at least one magnet of theplurality of magnets.

In accordance with a tenth aspect of the present disclosure, which maybe used in combination with any other aspect or combination of aspectslisted herein, the sliding device includes a base portion and a magnetholder, wherein the base portion is moveable along the guide rail, andthe magnet holder is separately moveable with respect to the baseportion.

In accordance with an eleventh aspect of the present disclosure, whichmay be used in combination with any other aspect or combination ofaspects listed herein, the plurality of magnets is positioned in an arcthat corresponds to an arc of the plurality of cuvettes located on therotor.

In accordance with a twelfth aspect of the present disclosure, which maybe used in combination with any other aspect or combination of aspectslisted herein, a system for washing a plurality of fluid samplesrespectively located within a plurality of cuvettes includes a holder tohold the plurality of cuvettes, a traveler mechanism configured totranslate upwardly towards the plurality of cuvettes held by the holderand position a plurality of magnets adjacent to the plurality ofcuvettes so that each cuvette of the plurality of cuvettes has a firstmagnet of the plurality of magnets adjacent to a first side and a secondmagnet of the plurality of magnets adjacent to an opposite second side,thereby suspending magnetic particles located within each of theplurality of cuvettes, and a wash system configured to translatedownwardly towards the plurality of cuvettes held by the holder so as toposition a probe within each of the plurality of cuvettes while theplurality of magnets suspend the magnetic particles located within eachof the plurality of cuvettes.

In accordance with a thirteenth aspect of the present disclosure, whichmay be used in combination with any other aspect or combination ofaspects listed herein, the system includes a rotor, the rotor includingthe holder, and the rotor is configured to rotate the plurality ofcuvettes about an axis to position the cuvettes over the travelersystem.

In accordance with a fourteenth aspect of the present disclosure, whichmay be used in combination with any other aspect or combination ofaspects listed herein, the axis of rotation of the rotor is a verticalaxis, and wherein the traveler mechanism is configured to translateupwardly parallel to the vertical axis.

In accordance with a fifteenth aspect of the present disclosure, whichmay be used in combination with any other aspect or combination ofaspects listed herein, the traveler mechanism includes a guide rail anda sliding device, and wherein the sliding device translates along theguide rail to position the plurality of magnets adjacent to theplurality of cuvettes.

In accordance with a sixteenth aspect of the present disclosure, whichmay be used in combination with any other aspect or combination ofaspects listed herein, a method of washing a plurality of fluid samplesrespectively located within a plurality of cuvettes includes addingmagnetic particles to the plurality of cuvettes, rotating the pluralityof cuvettes over a plurality of magnets, raising the plurality ofmagnets so that each cuvette of the plurality of cuvettes has a firstmagnet of the plurality of magnets adjacent to a first side and a secondmagnet of the plurality of magnets adjacent to an opposite second side,suspending the magnetic particles in the plurality of cuvettes with theplurality of magnets, lowering a plurality of probes so that eachcuvette of the plurality of cuvettes has a probe of the plurality ofprobes located therein, and aspirating fluid from each cuvette of theplurality of cuvettes with a respective probe.

In accordance with a seventeenth aspect of the present disclosure, whichmay be used in combination with any other aspect or combination ofaspects listed herein, raising the magnets includes positioning a magnethaving a first polarity adjacent to the first side and a magnet havingan opposite second polarity adjacent to the second side.

In accordance with a eighteenth aspect of the present disclosure, whichmay be used in combination with any other aspect or combination ofaspects listed herein, the method includes raising the plurality ofprobes away from the cuvettes and detecting if one or more of the probesbecomes misaligned.

In accordance with a nineteenth aspect of the present disclosure, whichmay be used in combination with any other aspect or combination ofaspects listed herein, the method includes locking the cuvettes into arotor with a removeable lid.

In accordance with a twentieth aspect of the present disclosure, whichmay be used in combination with any other aspect or combination ofaspects listed herein, the method includes raising the plurality ofmagnets and lowering the plurality of probes in directions parallel to arotational axis of the cuvettes.

Unless otherwise indicated, all numbers expressing quantities ofingredients, properties such as molecular weight, reaction conditions,and so forth used in the specification and claims are to be understoodas being modified in all instances by the term “about.” As used hereinthe terms “about” and “approximately” means within 10 to 15%, preferablywithin 5 to 10%. Accordingly, unless indicated to the contrary, thenumerical parameters set forth in the specification and attached claimsare approximations that may vary depending upon the desired propertiessought to be obtained by the present invention. At the very least, andnot as an attempt to limit the application of the doctrine ofequivalents to the scope of the claims, each numerical parameter shouldat least be construed in light of the number of reported significantdigits and by applying ordinary rounding techniques. Notwithstandingthat the numerical ranges and parameters setting forth the broad scopeof the invention are approximations, the numerical values set forth inthe specific examples are reported as precisely as possible. Anynumerical value, however, inherently contains certain errors necessarilyresulting from the standard deviation found in their respective testingmeasurements.

The terms “a,” “an,” “the” and similar referents used in the context ofdescribing the invention (especially in the context of the followingclaims) are to be construed to cover both the singular and the plural,unless otherwise indicated herein or clearly contradicted by context.Recitation of ranges of values herein is merely intended to serve as ashorthand method of referring individually to each separate valuefalling within the range. Unless otherwise indicated herein, eachindividual value is incorporated into the specification as if it wereindividually recited herein. All methods described herein can beperformed in any suitable order unless otherwise indicated herein orotherwise clearly contradicted by context. The use of any and allexamples, or exemplary language (e.g., “such as”) provided herein isintended merely to better illuminate the invention and does not pose alimitation on the scope of the invention otherwise claimed. No languagein the specification should be construed as indicating any non-claimedelement essential to the practice of the invention.

Groupings of alternative elements or embodiments of the inventiondisclosed herein are not to be construed as limitations. Each groupmember may be referred to and claimed individually or in any combinationwith other members of the group or other elements found herein. It isanticipated that one or more members of a group may be included in, ordeleted from, a group for reasons of convenience and/or patentability.When any such inclusion or deletion occurs, the specification is deemedto contain the group as modified thus fulfilling the written descriptionof all Markush groups used in the appended claims.

Certain embodiments of this invention are described herein, includingthe best mode known to the inventors for carrying out the invention. Ofcourse, variations on these described embodiments will become apparentto those of ordinary skill in the art upon reading the foregoingdescription. The inventor expects skilled artisans to employ suchvariations as appropriate, and the inventors intend for the invention tobe practiced otherwise than specifically described herein. Accordingly,this invention includes all modifications and equivalents of the subjectmatter recited in the claims appended hereto as permitted by applicablelaw. Moreover, any combination of the above-described elements in allpossible variations thereof is encompassed by the invention unlessotherwise indicated herein or otherwise clearly contradicted by context.

Specific embodiments disclosed herein may be further limited in theclaims using consisting of or consisting essentially of language. Whenused in the claims, whether as filed or added per amendment, thetransition term “consisting of” excludes any element, step, oringredient not specified in the claims. The transition term “consistingessentially of” limits the scope of a claim to the specified materialsor steps and those that do not materially affect the basic and novelcharacteristic(s). Embodiments of the invention so claimed areinherently or expressly described and enabled herein.

Furthermore, numerous references have been made to patents and printedpublications throughout this specification. Each of the above-citedreferences and printed publications are individually incorporated hereinby reference in their entirety.

In closing, it is to be understood that the embodiments of the inventiondisclosed herein are illustrative of the principles of the presentinvention. Other modifications that may be employed are within the scopeof the invention. Thus, by way of example, but not of limitation,alternative configurations of the present invention may be utilized inaccordance with the teachings herein. Accordingly, the present inventionis not limited to that precisely as shown and described.

The invention is claimed as follows:
 1. A method of washing a pluralityof cuvettes each containing a fluid sample, the method comprising:adding magnetic particles to the plurality of cuvettes, the plurality ofcuvettes located in a rotor configured to rotate the plurality ofcuvettes about a vertical axis; rotating, via the rotor, the pluralityof cuvettes over a traveler mechanism, the traveler mechanism locatedbeneath the rotor, the traveler mechanism including: a guide railprovided in a vertical orientation with respect to the rotor, a slidingdevice configured to vertically translate along the guide rail, and amagnet holder connected to the sliding device, the magnet holderconfigured to retain a plurality of magnets that are spaced apart at adistance to enable a respective cuvette to pass between adjacentmagnets, wherein the sliding device is configured to translatevertically toward the rotor; raising the plurality of magnets via thetraveler mechanism so that each cuvette of the plurality of cuvettes hasa first magnet of the plurality of magnets adjacent to a first side anda second magnet of the plurality of magnets adjacent to an oppositesecond side; causing the magnetic particles to be suspended in theplurality of cuvettes with the plurality of magnets; lowering aplurality of probes so that each cuvette of the plurality of cuvetteshas a probe of the plurality of probes located therein; and aspiratingfluid from each cuvette of the plurality of cuvettes with a respectiveprobe.
 2. The method of claim 1, wherein the plurality of probes areincluded within a wash mechanism that is located above the rotor, thewash mechanism including: an arm configured to be movable vertically andhorizontally with respect to the rotor to enable lowering the pluralityof probes; a plurality of tubes supported by the arm and connected to atleast one fluid supply; and a base connected to an end of the arm, thebase configured to retain the plurality of probes that are each fluidlyconnected to one of the plurality of tubes to enable aspirating thefluid from each cuvette of the plurality of cuvettes.
 3. The method ofclaim 2, wherein aspirating the fluid from each cuvette of the pluralityof cuvettes includes causing the plurality of probes, via the pluralityof tubes, to wash the fluid sample within each of the plurality ofcuvettes by at least one of injecting fluid into or aspirating fluidfrom the plurality of cuvettes when the arm is horizontally aligned withthe plurality of cuvettes and translated vertically to place at least aportion of the plurality of probes respectively into the plurality ofcuvettes.
 4. The method of claim 3, wherein the plurality of probes islowered while the plurality of magnets suspend the magnetic particlesand the bound fluid sample located within each of the plurality ofcuvettes.
 5. The method of claim 3, wherein aspirating the fluid isperformed using a first section of each respective probe and injectingthe fluid is performed using a second section of each respective probe.6. The method of claim 3, further comprising heating at least one of theinjected fluid or the aspirated fluid via a heater in proximity to theplurality of tubes.
 7. The method of claim 1, further comprisingtranslating vertically the sliding device away from the rotor after thesuspension of the magnetic particles is no longer needed.
 8. The methodof claim 1, wherein raising the magnets includes positioning a magnethaving a first polarity adjacent to the first side and a magnet havingan opposite second polarity adjacent to the second side.
 9. The methodof claim 1, further comprising raising the plurality of probes away fromthe cuvettes after aspirating the fluid.
 10. The method of claim 1,further comprising detecting, via a probe positioning sensor, if one ormore of the probes becomes misaligned when lowering the plurality ofprobes.
 11. The method of claim 1, further comprising causing theplurality of cuvettes to be locked into the rotor using a removable lid.12. The method of claim 1, further comprising raising the plurality ofmagnets and lowering the plurality of probes in directions parallel tothe vertical axis.
 13. The method of claim 1, further comprising causinga locking mechanism of the traveler mechanism to engage a protrusionlocated on an underside of the rotor to hold the traveler mechanism inplace when the plurality of cuvettes is located adjacent to theplurality of magnets.
 14. The method of claim 1, wherein the fluidincludes a wash buffer and the fluid sample includes at least one of areagent, a conjugate sample, or luminescent label.
 15. A method ofwashing a plurality of cuvettes each containing a fluid sample, themethod comprising: adding magnetic particles to the plurality ofcuvettes, the plurality of cuvettes located in a rotor configured torotate the plurality of cuvettes about a vertical axis; rotating, viathe rotor, the plurality of cuvettes over a traveler mechanism, thetraveler mechanism located beneath the rotor, the traveler mechanismincluding: a guide rail provided in a vertical orientation with respectto the rotor, a sliding device configured to vertically translate alongthe guide rail, and a magnet holder connected to the sliding device, themagnet holder configured to retain a plurality of magnets that arespaced apart at a distance to enable a respective cuvette to passbetween adjacent magnets, wherein the sliding device is configured totranslate vertically toward the rotor; raising the plurality of magnetsvia the traveler mechanism so that each cuvette of the plurality ofcuvettes has a first magnet of the plurality of magnets adjacent to afirst side and a second magnet of the plurality of magnets adjacent toan opposite second side; and causing the magnetic particles to besuspended in the plurality of cuvettes with the plurality of magnets forwashing.
 16. The method of claim 15, wherein washing includes: loweringa plurality of probes so that each cuvette of the plurality of cuvetteshas a probe of the plurality of probes located therein; and at least oneof injecting fluid into or aspirating fluid from the plurality ofcuvettes via the plurality of probes.
 17. The method of claim 16,wherein the plurality of probes is lowered via a wash mechanism that islocated above the rotor, the wash mechanism including: an arm configuredto be movable vertically and horizontally with respect to the rotor toenable lowering the plurality of probes; a plurality of tubes supportedby the arm and connected to at least one fluid supply; and a baseconnected to an end of the arm, the base configured to retain theplurality of probes that are each fluidly connected to one of theplurality of tubes.
 18. The method of claim 17, wherein the washingoccurs after the arm is horizontally aligned with the plurality ofcuvettes and translated vertically to place at least a portion of theplurality of probes respectively into the plurality of cuvettes.
 19. Themethod of claim 16, wherein the plurality of probes is lowered while theplurality of magnets suspend the magnetic particles and the bound fluidsample located within each of the plurality of cuvettes, and whereinaspirating the fluid is performed using a first section of eachrespective probe and injecting the fluid is performed using a secondsection of each respective probe.
 20. The method of claim 15, whereinthe fluid includes a wash buffer and the fluid sample includes at leastone of a reagent, a conjugate sample, or luminescent label.